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- Title
Tumor-penetrating nanoplatform with ultrasound “unlocking” for cascade synergistic therapy and visual feedback under hypoxia.
- Authors
Xie, Zhuoyan; Wang, Junrui; Luo, Yuanli; Qiao, Bin; Jiang, Weixi; Zhu, Leilei; Ran, Haitao; Wang, Zhigang; Zhu, Wei; Ren, Jianli; Zhou, Zhiyi
- Abstract
Background: Combined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy. Results: A visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named tLyP-1H(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with 1O2 produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O2 supply in vitro, and achieve significant tumor inhibition in vivo. Conclusion: We present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O2 supply, which ultimately synergistically enhanced cascade therapy.
- Publication
Journal of Nanobiotechnology, 2023, Vol 21, Issue 1, p1
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/s12951-023-01765-x